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In a preceding paper we reported the evolution of chagasic cardiopathy in mice inoculated with low number of T. cruzi from 2 days to 75 days post-infection (p.i.). The present work analyzed the contractility, pharmacological response and histopathology of myocardium isolated from chronic chagasic mice from 90 days until 180 days. p.i. Myocardium contractile force reached values similar to controls until 165 days p.i. From this to the end contractility was significantly lower. At 90 days p.i. NE provoked negative inotropic effect or had no effect in 13% of the cases tested. The others had a reactivity to NE similar to normal ventricles. From 105 days until 180 days p.i. NE induced to a positive inotropic effect significantly lower than in normal. ACh effect was significantly smaller from 165 days to the end. Previously ACh ventricles responses were as control. The effects of dibenamine, propranolol and atropine (10-6M) on chagasic ventricles were similar to those observed in normal tissues. At 90 days p.i. the histopathology showed focalized inflammatory infiltrates. At 180 days p.i. fibers fragmentations and loss of typical striated characteristic of cardiac tissue. The abnormal pharmacological response described could be attributed to alterations in cardiac beta and muscarinic receptors probably due to a lower oxygen support. The present paper shows that during chronic Chagas' disease myocardial function and pharmacological reactivity are seriously and definitively compromised.

Cardiac disease is usually the most serious complication of human infection with Trypanosoma cruzi in our country. This report studies the evolution of the chagasic cardiopathy in mice inoculated with low number of parasites during acute and indeterminate stages in different aspects: contractility, histopathology and pharmacological response. From 2-45 days post infection (p.i.) (acute stage) myocardium contractile force reached higher values than in controls, but norepinephrine (NE) response was significantly lower. Acetylcholine (ACh) caused a negative inotropic effect similar to the observed in control group. In this period cardiac damage evolved to an acute interstitial myocarditis. In the indeterminate phase (45-75 days p.i.) of this parasitosis NE produced either small inotropic effect, negative inotropic effect or had no effect on the ventricles tested. A significantly low ACh effect, sub-endocardiac perivascular fibrosis and necrosis in wall bases were also observed. The abnormal pharmacological response described could be ascribed to modifications in cardiac beta and muscarinic receptors number or affinity. The present results showed that in myocardium isolated from T. cruzi infected mice the histopathology, contractility and pharmacological response were altered from 48 h p.i. reaching a maximum disorder at 60 days p.i.

The isometric developed tension (IDT) and the pharmacological response of isolated myocardium from T. cruzi infected Albino Swiss mice in the acute and chronic Chagas' disease, were studied. The animals were infected with 7 X 10(4) trypomastigotes, form of T. cruzi, Tulahuen strain for the acute infection and with 45 parasites for the chronic stage. The isolated myocardium from acute and chronic chagasic mice reached IDT levels similar to normal hearts. The addition of norepinephrine (NE) to acute ventricles led to lower IDT values than in control group; this hyporeactivity to NE was absent in the chronic stage. On the other hand, epinephrine (EPI) effects on acute and chronic ventricles lead to significantly higher IDT values when compared with their controls. Propranolol blocked the higher effect of EPI in isolated myocardium from the acute stage, but the hyperreactivity described in the chronic stage could not be inhibited by the beta receptors antagonist. The agonist and antagonist tested act on cardiac plasma membrane beta receptors and their actions modify transmembrane calcium fluxes, so that the present study shows that Chagas' disease modifies the normal behavior of adrenergic beta cardiac receptors in different degree depending on the stage of the trypanosomiasis.

The effects of different pharmacological agents on the isometric developed tension (IDT) of right ventricles isolated from chronic chagasic C3HS mice were studied. The IDT in ventricles of chagasic animals was lower than in ventricles of normal mice (P less than 0.01). Chagasic ventricles exhibited hyperreactivity to norepinephrine but not to epinephrine. This hyperreactivity was masked by propranolol and not by dibenamine. Acetylcholine produced a reduction of IDT to similar values in normal and chagasic myocardia. The possibility that the effect of the drugs tested might not result from specially beta adrenoceptor-mediated reactions, but from alterations at other cellular sites is discussed.